crossing96/oncoscreening huggingface dataset:
Screening of MicroRNA Biomarkers Related to the Progression of Bladder Cancer.	Objective: This study aimed to identify the novel microRNAs (miRNAs) for early diagnosis of bladder cancer. Materials and Methods: Differentially expressed miRNAs between early and advanced bladder cancer were identified by differential expression analysis, using miRNA-seq data from The Cancer Genome Atlas (TCGA). The optimal subset of feature miRNAs for pathologic stage prediction was acquired by Random Forest algorithm and was used to construct a support vector machine (SVM) classifier. The performance of the SVM classifier in predicting the progression of bladder cancer samples was validated using an independent validating dataset. An miRNA-regulated target gene network was finally constructed and functional annotation were performed for the target genes. Results: A total of 52 significantly differentially expressed miRNAs were identified between early and advanced bladder cancer samples and 17 of these miRNAs were identified to be feature miRNAs. The 17 feature miRNAs were used to construct an SVM classifier, which showed a high performance in pathologic stage prediction for both training and validating dataset. Besides, our functional annotation analysis showed that the feature miRNAs were significantly involved in biological processes and pathways related to extracellular matrix process and PI3K/Akt signaling. Conclusions: The optimal subset of miRNAs may act as potential therapeutic targets and diagnostic markers of bladder cancer.	bladder
Identification of low-frequency variants of UGT1A3 associated with bladder cancer risk by next-generation sequencing.	Although genome-wide association studies (GWASs) have successfully revealed many common risk variants for bladder cancer, the heritability is still largely unexplained. We hypothesized that low-frequency variants involved in bladder cancer risk could reveal the unexplained heritability. Next-generation sequencing of 113 patients and 118 controls was conducted on 81 genes/regions of known bladder cancer GWAS loci. A two-stage validation comprising 3,350 cases and 4,005 controls was performed to evaluate the effects of low-frequency variants on bladder cancer risk. Biological experiments and techniques, including electrophoretic mobility shift assays, CRISPR/Cas9, RNA-Seq, and bioinformatics approaches, were performed to assess the potential functions of low-frequency variants. The low-frequency variant rs28898617 was located in the first exon of UGT1A3 and was significantly associated with increased bladder cancer risk (odds ratio = 1.50, P = 3.10 × 10(-6)). Intriguingly, rs28898617 was only observed in the Asian population, but monomorphism was observed in the European population. The risk-associated G allele of rs28898617 increased UGT1A3 expression, facilitated UGT1A3 transcriptional activity, and enhanced the binding activity. In addition, UGT1A3 deletion significantly inhibited the proliferation, invasion, and migration of bladder cancer cells and xenograft tumor growth. Mechanistically, UGT1A3 induced LAMC2 expression by binding CBP and promoting histone acetylation, which remarkably promoted the progression of bladder cancer. This is the first targeted sequencing study to reveal that the novel low-frequency variant rs28898617 and its associated gene UGT1A3 are involved in bladder cancer development, providing new insights into the genetic architecture of bladder cancer.	bladder
Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis.	Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle-related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.	bladder
Protocols for Preparation and Mass Spectrometry Analysis of Clinical Urine Samples to Identify Candidate Biomarkers of Schistosoma-Associated Bladder Cancer.	Advances in mass spectrometry instrumentation have revolutionized analytical capability in clinical proteomics. In parallel, various sample preparation methods have been developed to try to address the inherent complexity and dynamic range of clinical samples, typically involving a combination of depletion of abundant proteins followed by extensive prefractionation. However, the depth of coverage routinely achieved in discovery proteomics experiments on peripheral fluids such as serum, still leaves something to be desired, especially if no depletion or prefractionation is done in order to increase the throughput of clinical samples. Remarkably, despite being an easily accessible, typically sterile and diagnostically rich clinical sample, urine is often overlooked and as such has received less development effort. As an ultrafiltrate of blood, urine contains proteins and protein fragments originating from all parts of the body which may have diagnostic or prognostic potential if accurately and reproducibly quantified. Here, we describe an efficient and simple method for the concentration of urine samples by methanol-chloroform precipitation and subsequent in-solution tryptic digestion prior to discovery or targeted mass spectrometry analysis. We exemplify this method by reference to the discovery of novel candidate urinary biomarkers of schistosomiasis. Importantly, the methods described here have been used to identify >1900 protein groups in human urine by label-free discovery proteomics, without requiring any prior depletion or prefractionation, making this approach amenable to high throughput clinical biomarker studies in many diseases.	bladder
Telomerase Activity Analysis In Urine Sediment for Bladder Cancer.	Bladder cancer with an incidence of 15 cases per 100,000 persons in the global population is the most common tumor of the urinary tract. Imaging techniques, cytoscopy, and cytology are not sufficiently accurate to detect early stage tumors, and the need for new diagnostic markers is still an urgency. Among the biomarkers most recently proposed to improve diagnostic accuracy and especially sensitivity, increasing attention has been focused on the role of the ribonucleoprotein, telomerase. Previous studies have shown that the quantitative telomerase repeat amplification protocol (TRAP) assay performed in voided urine is an important noninvasive tool for the diagnosis of bladder tumors since it has very high sensitivity and specificity, even for early stage and low-grade tumors. Telomerase activity in urine determined by TRAP seems to be marker of great potential, even more advantageous in cost-benefit terms when used in selected symptomatic patients or professionally high-risk subgroups. Here we report the real-time PCR protocol to detect telomerase activity in urine sediment for bladder cancer.	bladder
Urinary Biomarkers In Bladder Cancer.	Bladder cancer has a very high frequency of recurrence and therefore requires close clinical surveillance throughout its life, with cystoscopies and serial cytological examinations. These tests are both invasive and expensive, with considerable interpersonal and inter-institutional variability. Moreover, cytological examination used for the diagnosis of low-grade tumors has a low sensitivity; thus, there is an increasing focus on the research for new, accurate, urinary markers. Herein, the biological basis, methodologies, and diagnostic performance of biomarkers are discussed.	bladder
Fluorescence In Situ Hybridization in Urine Samples (UroVysion Kit).	Cystoscopy is considered the standard approach to the diagnostic workup of urinary symptoms. It has high sensitivity and specificity for papillary tumors of the bladder but low sensitivity and specificity for flat lesions. It is also expensive and may cause discomfort and complications. Urine cytology, in contrast, has the advantage of being a noninvasive test with high specificity but suffers from low sensitivity in low-grade and early-stage tumors, possibly due to the low number of exfoliated cells in urine. Numerous new noninvasive tests have been proposed. Among these, fluorescence in situ hybridization (FISH) has been studied for long time and in 2005 UroVysion Bladder Cancer Kit (UroVysion Kit) (Abbott/Vysis) received FDA approval for initial diagnosis of bladder carcinoma in patients with hematuria and subsequent monitoring for tumor recurrence in patients previously diagnosed with bladder cancer. The UroVysion Kit is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus by FISH in urine specimens from symptomatic patients, those with hematuria suspected of having bladder cancer. Here, the approach for FISH assay by using UroVysion Bladder Cancer kit according to manufacturer's instructions is described.	bladder
Risk of bladder cancer in male Japanese workers exposed to ortho-toluidine and other aromatic amines.	PURPOSE: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). METHODS: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. RESULTS: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7-104.3) and apparent dose-response relationships were revealed between the SIR and the surrogate exposure level in the 0-10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose-response relationships were observed. CONCLUSIONS: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.	bladder
Circadian clock protein CRY1 prevents paclitaxel‑induced senescence of bladder cancer cells by promoting p53 degradation.	Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first‑line treatment is cisplatin‑based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy‑induced senescence can act as a 'back‑up' response to chemotherapy in cancer types that are resistant to apoptosis‑based anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)‑induced senescence in cisplatin‑resistant bladder cancer cells. Cisplatin‑resistant bladder cancer cells were established via long‑term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA‑β‑Gal staining, but this was not observed in the cisplatin‑resistant cells. The cisplatin‑resistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatin‑resistant cells, and that CRY1 knockdown restored PTX‑induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto‑oncogene. These data suggested that the accumulated CRY1 in cisplatin‑resistant cells could prevent PTX‑induced senescence by promoting p53 degradation.	bladder
[Penile metastasis from urothelial carcinoma: Review of literature.].	OBJECTIVE: Penile metastasis is a very rare clinical entity. The primary origin is usually genitourinar y followed by the gastrointestinal. MATERIAL AND METHODS: Review of the available literature on a case of penile metastasis of urothelial bladder carcinoma. RESULTS: Penile metastasis is an exceptional entity despite the rich vascularization of this organ. Less than 500 cases have been described. Most cases manifestas exophytic or nodular lesions. Its association with disseminated disease conditions its palliative management in a large part of the cases, as well as an unfavorable prognosis. In selected cases, surgical treatment can be chosen. CONCLUSIONS: Since its clinical presentation is variable, clinical suspicion is important in the presence of a skin lesion of torpid evolution taking into account the patient's oncological history.	bladder
Radionuclide-guided sentinel lymph node mapping in urachal cancer.	BACKGROUND: Urachal cancer gives metastases through the lymph nodes (LNs). No lymphadenectomy scheme in the case of this cancer exist, yet it is proposed as a staging procedure. An assessment of lymphatic outflow from the tumor site with the use of single-photon emission computed tomography/computed tomography (SPECT/CT) lymphangiography is possible for staging purposes. OBJECTIVES: To perform the mapping of the LNs draining the lymph from urachal cancer with the use of radioisotope-based technique and to propose the lymphadenectomy template in case of urachal cancer. MATERIAL AND METHODS: A prospective study was conducted in 5 patients with urachal cancer. The 99m-technetium (Tc-99m)-nanocolloid was injected during a cystoscopy prior to the surgery. Lymphangiography was performed using SPECT/CT. A radioactive LNs analysis with the use of a hand-held gamma-ray detection probe was conducted during the surgery and the sentinel lymph node (SLN) biopsy procedure was performed. An additional lymphadenectomy containing the lymphatic basin of identified radioactive LNs was performed. RESULTS: In all cases lymphatic outflow from the urachal tumor to the LNs was present. Preoperative SPECT/CT allowed detecting the activity of the radiotracer in the common iliac region in all the studied patients. In 3 cases, bilateral lymphatic outflow, and in 2 cases, unilateral lymphatic outflow was observed. All preoperatively visualized LNs were found and excised with the use of a gamma-ray detection probe during a lymphadenectomy. In all cases, SLNs did not contain metastases. CONCLUSIONS: Mapping of the LNs draining the lymph from urachal cancer with the use of radiotracer is possible. Lymphatic outflow in the case of this cancer can be both unilateral and bilateral. No recommendations about the extension of lymphadenectomy are proposed. We recommend individual assessment and treatment based on additional knowledge about lymphatic outflow. This allows for minimally invasive yet targeted treatment as an SLN basin lymphadenectomy.	bladder
Surgical challenges and considerations in Tri-modal therapy for muscle invasive bladder cancer.	Trimodal therapy (TMT) for muscle invasive bladder cancer has become an accepted alternative to radical cystectomy and has become integrated into national guidelines as standard a treatment option. The urologist plays a critical role in proper patient selection, thorough transurethral resection, ongoing cystoscopic surveillance and management of local recurrences. There exists multiple patient related and tumor related factors, which contribute to the selection of TMT vs. radical cystectomy for a patient with muscle invasive bladder cancer. Although the ideal patient for TMT has a tumor which can undergo a visibly complete resection, has no associated hydronephrosis, does not invade the prostatic urethra and is not associated with diffuse carcinoma in situ throughout the bladder, select patients who do not meet all these criteria can still be successfully treated with this approach. A multidisciplinary approach including urology, radiation oncology and medical oncology is paramount with clear communication of tumor location, timing of chemoradiation and repeat cystoscopic resection followed by surveillance. Nonmuscle invasive bladder cancer recurrences can occur in up to 26% of patients after completion of TMT, with many being treated by routine and standard therapy for non-muscle invasive bladder cancer. However, in this population after TMT, early salvage cystectomy should be considered in those with adverse features, including T1 disease, tumor greater than 3 cm, CIS, or lymphovascular invasion. Salvage cystectomy can be performed for local recurrences with acceptable oncologic control and no clear evidence of any greater risk of early complications; however, there may be a slightly increased risk for late complications, namely small bowel obstruction, ureteral stricture, and parastomal hernia. An understanding of these surgical considerations is of utmost importance to the treating urologist in selecting and managing a patient through TMT.	bladder
Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features.	Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.	bladder
Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients.	OBJECTIVE: To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. METHODS: This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. RESULTS: With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas' model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients' net benefit. CONCLUSIONS: This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.	bladder
A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture.	Bladder cancer is among the most prevalent cancers worldwide. Currently, few bladder cancer models have undergone thorough characterization to assess their fidelity to patient tumors, especially upon propagation in the laboratory. Here, we establish and molecularly characterize CoCaB 1, an aggressive cisplatin-resistant muscle-invasive bladder cancer patient-derived xenograft (PDX) and companion organoid system. CoCaB 1 was a subcutaneous PDX model reliably transplanted in vivo and demonstrated an acceleration in growth upon serial transplantation, which was reflected in organoid and 2D cell culture systems. Transcriptome analysis revealed progression towards an increasingly proliferative and stem-like expression profile. Gene expression differences between organoid and PDX models reflected expected differences in cellular composition, with organoids enriched in lipid biosynthesis and metabolism genes and deprived of extracellular components observed in PDXs. Both PDX and organoid models maintained the histological fidelity and mutational heterogeneity of their parental tumor. This study establishes the CoCaB 1 PDX and organoid system as companion representative tumor models for the development of novel bladder cancer therapies.	bladder